1. Field of the Invention
This invention relates to a novel method for the preparation of an N.sup.6 -substituted 3',5'-cyclic adenosine monophosphate (hereinafter referred to briefly as N.sup.6 -substituted CAMP) and a salt thereof.
2. Description of the Prior Art
The N.sup.6 -substituted CAMP is of high utility value as an important intermediate used in the synthesis of 6,8-disubstituted CAMP (U.S. Pat. No. 4,058,659) which has excellent pharmacological activities including antiinflammative, platelet aggregation inhibitory, hypotensive, and cardiotonic actions.
For the preparation of an N.sup.6 -substituted 8-thiobenzyl-CAMP, as an example among 6,8-disubstituted derivatives of CAMP, from an N.sup.6 -substituted CAMP, there is known a method described in Journal of Medicinal Chemistry, Vol. 23, 242-251 (1980).
Conventionally known methods of producing an N.sup.6 -substituted CAMP include a method which comprises deamination of CAMP with a nitrite to form inosine 3',5'-cyclic phosphate followed by chlorination with phosphorus oxychloride to 6-chloropurine-9-.beta.-D-ribofuranosyl-3',5'-cyclic phosphate which is then reacted with an alkylamine to yield an N.sup.6 -substituted CAMP [Biochemistry, Vol. 11, 2704-2709 (1972)] and another one which comprises the reaction of CAMP with a halide to form a 1-substituted CAMP followed by Dimroth rearrangement in an alkali solution to yield an N.sup.6 -substituted CAMP. Both of these methods, however, have disadvantages of complicated procedures, possible by-product formation, and low yields.